The Netherlands Heart Tissue Bank : Strengthening the cardiovascular research infrastructure with an open access Cardiac Tissue Repository.

AIM: Cardiac diseases remain a leading cause of cardiovascular disease (CVD) related hospitalisation and mortality. That is why research to improve our understanding of pathophysiological processes underlying cardiac diseases is of great importance. There is a strong need for healthy and diseased human cardiac tissue and related clinical data to accomplish this, since currently used animal and in vitro disease models do not fully grasp the pathophysiological processes observed in humans. This design paper describes the initiative of the Netherlands Heart Tissue Bank (NHTB) that aims to boost CVD-related research by providing an open-access biobank. METHODS: The NHTB, founded in June 2020, is a non-profit biobank that collects and stores biomaterial (including but not limited to myocardial tissue and blood samples) and clinical data of individuals with and without previously known cardiac diseases. All individuals aged ≥ 18 years living in the Netherlands are eligible for inclusion as a potential future donor. The stored samples and clinical data will be available upon request for cardiovascular researchers. CONCLUSION: To improve the availability of cardiac tissue for cardiovascular research, the NHTB will include extensive (cardiac) biosamples, medical images, and clinical data of donors with and without a previously known cardiac disease. As such, the NHTB will function as a translational bridge to boost a wide range of cardiac disease-related fundamental and translational studies.

The impact of implementing an endocarditis team in comparison to the classic heart team in a tertiary referral centre.

BACKGROUND: Infective endocarditis (IE) is a complex disease for which the European Society of Cardiology guideline recommends a dedicated multidisciplinary endocarditis team (ET) approach since 2015. It is currently unknown whether this ET approach is beneficial compared to a classic heart team approach including bedside consultation by an infectious disease specialist in Western Europe. METHODS: This retrospective single centre, observational cohort study was conducted at the Radboudumc, a tertiary referral centre in the Netherlands. Consecutive patients treated for IE were included from September 2017 to September 2018 before implementation of a dedicated ET and from May 2019 to May 2020 afterwards. RESULTS: In total, 90 IE patients (45 patients before and 45 patients after the implementation of the ET) were included. No significant differences were found in diagnostic workup, surgical treatment (surgery performed 69% vs. 71%, p = 0.82), time to surgery because of an urgent indication (median 4 vs. 6 days, p = 0.82), in-hospital complications (53% vs. 67%, p = 0.20), and 6-month mortality (11% vs. 13%, p = 0.75) between IE patients treated before and after the implementation of the ET. CONCLUSION: Formalization of the recommended multidisciplinary endocarditis team might not significantly improve the complication rate nor the short term outcome.

Cardiac function in relation to myocardial injury in hospitalised patients with COVID-19.

BACKGROUND: Previous studies have reported on myocardial injury in patients with coronavirus infectious disease 19 (COVID-19) defined as elevated cardiac biomarkers. Whether elevated biomarkers truly represent myocardial dysfunction is not known. The aim of this study was to explore the incidence of ventricular dysfunction and assess its relationship with biomarker analyses. METHODS: This cross-sectional study ran from April 1 to May 12, 2020, and consisted of all consecutively admitted patients to the Radboud university medical centre nursing ward for COVID-19. Laboratory assessment included high-sensitivity Troponin T and N­terminal pro-B-type natriuretic peptide (NT-proBNP). Echocardiographic evaluation focused on left and right ventricular systolic function and global longitudinal strain (GLS). RESULTS: In total, 51 patients were included, with a median age of 63 years (range 51-68 years) of whom 80% was male. Troponin T was elevated (>14 ng/l) in 47%, and a clinically relevant Troponin T elevation (10â€¯× URL) was found in three patients (6%). NT-proBNP was elevated (>300 pg/ml) in 24 patients (47%), and in four (8%) the NT-proBNP concentration was >1,000 pg/ml. Left ventricular dysfunction (ejection fraction <52% and/or GLS >-18%) was observed in 27%, while right ventricular dysfunction (TAPSE <17 mm and/or RV S' < 10 cm/s) was seen in 10%. There was no association between elevated Troponin T or NT-proBNP and left or right ventricular dysfunction. Patients with confirmed pulmonary embolism had normal right ventricular function. CONCLUSIONS: In hospitalised patients, it seems that COVID-19 predominantly affects the respiratory system, while cardiac dysfunction occurs less often. Based on a single echocardiographic evaluation, we found no relation between elevated Troponin T or NT-proBNP, and ventricular dysfunction. Echocardiography has limited value in screening for ventricular dysfunction.

Improved patient selection for cardiac resynchronization therapy by normalization of QRS duration to left ventricular dimension.

AIMS: This study evaluates the relative importance of two components of QRS prolongation, myocardial conduction velocity and travel distance of the electrical wave front (i.e. path length), for the prediction of acute response to cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB) patients. METHODS AND RESULTS: Thirty-two CRT candidates (ejection fraction <35%, LBBB) underwent cardiac magnetic resonance (CMR) imaging to provide detailed information on left ventricular (LV) dimensions. Left ventricular end-diastolic volume (LVEDV) was used as a primary measure for path length, subsequently QRSd was normalized to LV dimension (i.e. QRSd divided by LVEDV) to adjust for conduction path length. Invasive pressure-volume loop analysis at baseline and during CRT was used to assess acute pump function improvement, expressed as LV stroke work (SW) change. During CRT, SW improved by +38 ± 46% (P < 0.001). The baseline LVEDV was positively related to QRSd (R = 0.36, P = 0.044). Despite this association, a paradoxical inverse relation was found between LVEDV and SW improvement during CRT (R = -0.40; P = 0.025). Baseline unadjusted QRSd was found to be unrelated to SW changes during CRT (R = 0.16; P = 0.383), whereas normalized QRSd (QRSd/LVEDV) yielded a strong correlation with CRT response (R = 0.49; P = 0.005). Other measures of LV dimension, including LV length, LV diameter, and LV end-systolic volume, showed similar relations with normalized QRSd and SW improvement. CONCLUSION: Since normalized QRSd reflects myocardial conduction properties, these findings suggest that myocardial conduction velocity rather than increased path length mainly determines response to CRT. Normalizing QRSd to LV dimension might provide a relatively simple method to improve patient selection for CRT.

The relationship between terminal QRS distortion on initial ECG and final infarct size at 4months in conventional ST- segment elevation myocardial infarct patients.

BACKGROUND: In the Sclarovsky-Birnbaum Ischemia Severity Grading System for patients with ST-segment elevation myocardial infarction (STEMI), "Terminal QRS distortion" is considered as "Grade III". This evidence for most severe ischemia is associated with cardiovascular magnetic resonance imaging (CMR) markers of myocardial damage in the subacute phase. Our aim was to assess whether terminal QRS distortions on the initial electrocardiogram (ECG) is predictive for infarct size (IS) and left ventricular ejection fraction (LVEF) at 4months in anterior versus infarct locations. METHODS: Patient data of the HEBE, GIPS III and MAST, were pooled. ECGs of 411 STEMI patients were classified as absence (Grade II) or presence (Grade III) of terminal QRS distortion according to Sclarovsky-Birnbaum grading. CMR was performed at approximately 4months and included IS and LVEF. RESULTS: Grade III ischemia was present in 142 of 411 (35%) patients and was more frequently observed with inferior STEMI (P=0.01). In the total cohort and in anterior STEMI, no difference in LVEF or IS was observed between the two Grades. Whereas, in inferior STEMI Grade III was associated with a larger IS (P<0.01) and also, a trend towards a lower LVEF was observed (P=0.09). CONCLUSION: In inferior STEMI, terminal QRS distortion on the initial ECG is associated with a larger IS at approximately 4months, and can be used to identify a high-risk population in the acute phase. Also, a Grade III was associated with a trend towards a lower LVEF.

Coronary CT angiography in the elderly.

People over 75 years of age represent a specific group of patients for which the clinician is often in doubt about what to do, whether additional diagnostic workup is helpful or a primary medical approach would suffice. However, this patient population is less prone to the long-term effects of radiation burden or contrast medium-induced nephropathy, and therefore it may be especially worthwhile to use advanced imaging techniques such as contrast-enhanced CT in these patients. The following cases illustrate two common diagnostic problems, in which coronary CT angiography decided the clinical course.

Tissue characterization of acute lesions during cardiac magnetic resonance-guided ablation of cavo-tricuspid isthmus-dependent atrial flutter: a feasibility study.

AIMS: To characterize acute lesions during cardiac magnetic resonance (CMR)-guided radiofrequency (RF) ablation of cavo-tricuspid isthmus (CTI)-dependent atrial flutter by combining T2-weighted imaging (T2WI), T1 mapping, first-pass perfusion, and late gadolinium enhancement (LGE) imaging. CMR-guided catheter ablation offers a unique opportunity to investigate acute ablation lesions. Until present, studies only used T2WI and LGE CMR to assess acute lesions. METHODS AND RESULTS: Fifteen patients with CTI-dependent atrial flutter scheduled for CMR-guided RF ablation were prospectively enrolled. Directly after achieving bidirectional block of the CTI line, CMR imaging was performed using: T2WI (n = 15), T1 mapping (n = 10), first-pass perfusion (n = 12), and LGE (n = 12) imaging. In case of acute reconnection, additional RF ablation was performed. In all patients, T2WI demonstrated oedema in the ablation region. Right atrial T1 mapping was feasible and could be analysed with a high inter-observer agreement (r = 0.931, ICC 0.921). The increase in T1 values post-ablation was significantly lower in regions showing acute reconnection compared with regions without reconnection [37 ± 90 ms vs. 115 ± 69 ms (P = 0.014), and 3.9 ± 9.0% vs. 11.1 ± 6.8% (P = 0.022)]. Perfusion defects were present in 12/12 patients. The LGE images demonstrated hyper-enhancement with a central area of hypo-enhancement in 12/12 patients. CONCLUSION: Tissue characterization of acute lesions during CMR-guided CTI-dependent atrial flutter ablation demonstrates oedema, perfusion defects, and necrosis with a core of microvascular damage. Right atrial T1 mapping is feasible, and may identify regions of acute reconnection that require additional RF ablation.

Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

Staphylococcus lugdunensis infective endocarditis with perforation of the sinus of Valsalva: a case report.

Background: Staphylococcus lugdunensis endocarditis is a rare but fulminant disease. Case summary: A 74-year-old female with a history of asymptomatic severe aortic valve stenosis and permanent atrial fibrillation presented with acute onset of fever (39.0°C). Electrocardiogram showed diffuse ST-segment elevation. She was hospitalized for further analysis. All blood cultures were positive for Staphylococcus lugdunensis and antibiotic treatment was started. Transthoracic echocardiography (TTE) showed known aortic valve stenosis without clear signs of endocarditis. The following day, a transoesophageal echocardiogram (TEE) showed a new moderate aortic valve regurgitation, new pericardial effusion (PE), and a thickened sinus of Valsalva (SOV) consistent with endocarditis with paravalvular involvement. Positron emission tomography-computed tomography was consistent with aortic valve endocarditis with paravalvular expansion. The patient was transferred to a tertiary referral centre for surgical treatment. On admission, patient was in shock and a second TTE revealed a new systolic and diastolic flow through the SOV to the right ventricle indicating SOV perforation. Additionally, there was flow in the PE suggestive of perforation of one of the cardiac chambers or large vessels. Emergent surgery showed extended infection with SOV perforation and a large perforation of the right ventricle. Ultimately, patient died during the operation because of extensive infection and refractory shock. Conclusion: Staphylococcus lugdunensis endocarditis is a severe disease with poor response to conventional anti-microbial treatment, destructive complications requiring surgery, and has a high mortality risk.

Metal artifact reduction in computed tomography: Is it of benefit in evaluating sacroiliac joint fusion?

PURPOSE: The aim of this study was to compare image quality of computed tomography (CT) images with and without orthopedic metal artifact reduction (O-MAR) in the follow-up of patients after sacroiliac (SI) joint fusion. METHODS: Thirty-six consecutive patients (31 females and 5 males) undergoing CT within 24 h after SI joint fusion were included. CT images were reconstructed with and without O-MAR and scored by two radiologists with over 20 years of experience using a six-point ordinal scale. Images were scored on overall image quality and five criteria that are important to the clinician for the follow-up of patients after SI joint fusion. In addition, images were scored on how well four bony structures could be delineated. Wilcoxon signed-ranks tests with Holm-Bonferroni correction were used to test for differences between the radiologists' scores on CT images with and without O-MAR. RESULTS: Both radiologists scored overall image quality significantly higher (p < 0.05) on the images without O-MAR than on the images with O-MAR. In addition, two of the follow-up criteria, delineation of the sacrum and delineation of the implanted ilium were scored significantly higher (p < 0.05) on the images without O-MAR. Neither radiologist scored the images with O-MAR significantly higher than the images without O-MAR for any of the criteria. CONCLUSION: CT imaging without O-MAR provided higher image quality and better assessment of SI joint fusion follow-up criteria compared to CT imaging with O-MAR in the follow-up of patients after SI joint fusion.

What is the long-term clinical outcome after fragility fractures of the pelvis? - A CT-based cross-sectional study.

BACKGROUND: Recently, Rommens and Hoffman introduced a CT-based classification system for fragility fractures of the pelvis (FFP). Although fracture characteristics have been described, the relationship with clinical outcome is lacking. The purpose of this study was to get insight into the type of treatment and subsequent clinical outcome after all types of FFP. METHODS: A cross-sectional cohort study was performed including all elderly patients (≥ 65 years) with a CT-diagnosed FFP, between 2007-2019 in two level 1 trauma centers. Data regarding treatment, mortality and clinical outcome was gathered from the electronic patient files. Patients were asked to complete patient-reported outcome measures (PROMs) regarding physical functioning (SMFA) and quality of life (EQ-5D). Additionally, a standardized multidisciplinary treatment algorithm was constructed. RESULTS: A total of 187 patients were diagnosed with an FFP of whom 117 patients were available for follow-up analysis and 58 patients responded. FFP type I was most common (60%), followed by type II (27%), type III (8%) and type IV (5%). Almost all injuries were treated non-operatively (98%). Mobility at six weeks ranged from 50% (type III) to 80% type II). Mortality at 1 year was respectively 16% (type I and II), 47% (type III) and 13% (type IV). Physical functioning (SMFA function index) ranged from 62 (type III and IV) to 69 (type II) and was significantly decreased (P=<0.001) compared to the age-matched general population. Quality of life was also significantly decreased, ranging from 0.26 (type III) to 0.69 (type IV). CONCLUSIONS: FFP type I and II are most common. Treatment is mainly non-operative, resulting in good mobility after six weeks, especially for patients with FFP type I and II. Mortality rates at one year were substantial in all patients. Physical functioning and quality of life was about 20-30% decreased compared to the general population.

Right atrial and ventricular strain detects subclinical changes in right ventricular function in precapillary pulmonary hypertension.

Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension (pPH) patients, but is insensitive to early changes. Strain might provide incremental information. In this study, we compare right atrial (RA) and RV strain in pPH patients to healthy controls, and evaluate the prognostic value of strain in pPH. In this cross-sectional study, 45 pPH patients and 20 healthy controls underwent CMR, and feature-tracking derived RA and RV strain were evaluated. pPH patients had impaired RA reservoir and conduit strain, and RV longitudinal strain (LS), compared to healthy controls. In pPH patients with preserved RVEF (≥ 50%, n = 18), RA reservoir (35% ± 9 vs. 41% ± 6, p = 0.02) and conduit strain (16% ± 8 vs. 23% ± 5, p = 0.004), and RV-LS (-25% ± 4 vs. -31% ± 4, p < 0.001) remained impaired, compared to healthy controls. The association of strain with the primary endpoint (combination of all-cause death, lung transplantation, and heart failure hospitalization) was evaluated using a multivariable Cox regression model. RV-LS (HR 1.18, 95%-CI 1.04-1.34, p = 0.01) and RA strain (reservoir: HR 0.87, 95%-CI 0.80-0.94, p = 0.001; conduit: HR 0.85, 95%-CI 0.75-0.97, p = 0.02, booster: HR 0.81, 95%-CI 0.71-0.92, p = 0.001) were independent predictors of outcome, beyond clinical and imaging features. In conclusion, pPH patients have impaired RA strain and RV-LS, even when RVEF is preserved. In addition, RA strain and RV-LS were independent predictors of adverse prognosis. These results emphasize the incremental value of RA and RV strain analyses, to detect alterations in RV function, even before RVEF declines.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

Comparison between myocardial function assessed by echocardiography during hospitalization for COVID-19 and at 4 months follow-up.

In patients hospitalized for corona virus infectious disease 19 (COVID-19) it is currently unknown whether myocardial function changes after recovery and whether this is related to elevated cardiac biomarkers. In this single center, prospective cohort study we consecutively enrolled hospitalized COVID-19 patients between 1 April and 12 May 2020. All patients underwent transthoracic echocardiography (TTE) evaluation during hospitalization and at a median of 131 days (IQR; 116-136) follow-up. Of the 51 patients included at baseline, 40 (age: 62 years (IQR; 54-68), 78% male) were available for follow-up TTE. At baseline, 68% of the patients had a normal TTE, regarding left ventricular (LV) and right ventricular (RV) volumes and function, compared to 83% at follow-up (p = 0.07). Median LV ejection fraction (60% vs. 58%, p = 0.54) and tricuspid annular plane systolic excursion (23 vs 22 mm, p = 0.18) were comparable between hospitalization and follow-up, but a significantly lower RV diameter (39 vs. 34 mm, p = 0.002) and trend towards better global longitudinal strain (GLS) (- 18.5% vs - 19.1%, p = 0.07) was found at follow-up. Subgroup analysis showed no relation between patients with and without elevated TroponinT and/or NT-proBNP during hospitalization and myocardial function at follow-up. Although there were no significant differences in individual myocardial function parameters at 4 months follow-up compared to hospitalisation for COVID-19, there was an overall trend towards normalization in myocardial function, predominantly due to a higher rate of normal GLS at follow-up.

'No-reflow' after acute myocardial infarction: direct visualisation of microvascular obstruction by gadolinium-enhanced CMR.

Cardiovascular magnetic resonance is considered the standard imaging modality in clinical trials to monitor patients after acute myocardial infarction. However, limited data are available with respect to infarct size, presence and extent of microvascular injury (MVO) and changes over time, in relation to cardiac function in optimally treated patients. In the current study we prospectively investigate the change of infarct size over time, and the incidence and significance of MVO in a uniform, optimally treated patient group after AMI. (Neth Heart J 2008;16:179-81.).

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J 2008;16:436-9.).